Search Results (43)

Background: Mitochondrial dysfunction is central to the pathogenesis of acute myocardial infarction (AMI), but mitochondria-related molecular biomarkers and mechanisms remain incompletely defined. This study aimed to identify mitochondria-associated biomarkers in AMI and elucidate their functional roles in mitochondrial dynamics, extracellular matrix (ECM) remodeling, and cardiac protection. Methods: Two GEO datasets (GSE19322, GSE71906) were analyzed to identify mitochondria-related differentially expressed genes (DE-MRGs) by intersecting DEGs with MitoCarta3.0 genes. Functional enrichment (GO/KEGG), LASSO regression, ROC curves, and nomogram modeling were employed to screen biomarkers. Immune infiltration profiling, GeneMANIA, GSEA, TF-mRNA and ceRNA network construction, and drug prediction analyses were performed. Expression validation was conducted via RT-qPCR, Western blot (WB), and immunohistochemistry (IHC) in murine AMI models and hypoxia-induced cardiomyocytes. Functional assays assessed cardiac performance (echocardiography), infarct size (TTC staining), fibrosis (Masson/Sirius red), oxidative stress (ROS), and ECM remodeling (MMP9/TIMP1 axis). Results: We identified 295 DE-MRGs, enriched in oxidative phosphorylation and mitochondrial metabolic pathways. Machine learning and validation analyses pinpointed MTFP1 and DNAJC28 as AMI biomarkers with strong diagnostic accuracy. In vivo and in vitro studies confirmed marked downregulation of MTFP1 post-AMI and under hypoxia. AAV9-mediated MTFP1 overexpression improved cardiac function, reduced infarct size, attenuated fibrosis, and decreased ROS levels. Mechanistically, MTFP1 upregulated phosphorylated DRP1 (Ser616) without altering total DRP1, balanced MMP9/TIMP1 activity, and suppressed fibrosis markers (COL1A1, α-SMA). Gelatin zymography indicated that MMP9 activation remained restrained despite elevated pro-MMP9, consistent with TIMP1-mediated regulation. Hypoxia-induced cardiomyocytes showed similar antifibrotic and antioxidative responses following MTFP1 overexpression. Conclusions: Our study identified MTFP1 as a novel mitochondria-related biomarker and therapeutic modulator in AMI. MTFP1 exerts cardioprotective effects by restoring mitochondrial fission balance and ECM remodeling through the p-DRP1/MMP9/TIMP1 signaling axis, attenuating fibrosis and oxidative stress. These findings provide mechanistic insight into mitochondria-targeted cardioprotection and highlight MTFP1 as a promising diagnostic and therapeutic target for AMI. Full article

Background: Stereotactic body radiotherapy (SBRT) for prostate cancer delivers high doses in few fractions but poses challenges in sparing adjacent organs at risk (OARs), particularly the intra-prostate urethra, bladder, rectum and penile bulb. Magnetic resonance-guided radiotherapy (MRgRT) using MR-Linac offers superior soft-tissue visualization and daily adaptive planning, potentially reducing OAR dose while maintaining target coverage. This study aimed to compare dose–volume parameters among MR-Linac (ML), volumetric modulated arc therapy (VMAT), and Tomotherapy (HT) plans for prostate SBRT. Methods: Thirty patients with localized prostate cancer were retrospectively analyzed. For each patient, three plans were generated: ML, VMAT and HT, using identical prescription and planning objectives. Dose–volume histogram (DVH) metrics were evaluated for clinical target volume (CTV), planning target volume (PTV), and OARs. Statistical comparisons were performed using non-parametric Friedman’s Test with post hoc Bonferroni test, with significance set at a p < 0.05. Results: CTV coverage was comparable across all modalities. ML achieved significantly higher PTV Dmin and near-maximum doses compared to VMAT and HT. Notably, ML provided substantial urethral sparing, reducing Dmax and Dmean by approximately 3.3 Gy compared to both VMAT and HT (p < 0.001). Rectal dose metrics were also lower with ML, while bladder and penile bulb doses showed minor increases (<3.5 Gy), considered clinically negligible. Femoral head doses were reduced in ML plans. Conclusions: MR-Linac planning for prostate SBRT offers meaningful dosimetric advantages, particularly in intra-prostate urethra urethral dose reduction, without compromising target coverage. These findings support incorporating MR-guided adaptive workflows into SBRT protocols to enhance OAR protection and potentially reduce treatment-related toxicity. Full article

Oesophageal cancer remains a significant global health burden with poor survival outcomes despite multimodal treatment. Recent advances in magnetic resonance imaging (MRI) have opened opportunities to improve radiotherapy delivery. This review examines the role of MRI and MR-guided radiotherapy (MRgRT) in oesophageal cancer, focusing on applications in staging, treatment planning, and response assessment, with particular emphasis on magnetic resonance linear accelerator (MR-Linac)-based delivery. Compared to computed tomography (CT), MRI offers superior soft-tissue contrast, enabling more accurate tumour delineation and the potential for reduced treatment margins. Real-time MR imaging during treatment can facilitate motion management, while daily adaptive planning can accommodate anatomical changes throughout the treatment course. Functional MRI sequences, including diffusion-weighted and dynamic contrast-enhanced imaging, offer quantitative data for treatment response monitoring. Early clinical and dosimetric studies demonstrate that MRgRT can significantly reduce radiation dose to critical organs while maintaining target coverage. However, clinical evidence for MRgRT in oesophageal cancer is limited to small early-phase studies, with no phase II/III trials demonstrating improvements in survival, toxicity, or patient-reported outcomes. Long-term clinical benefits and cost-effectiveness remain unproven, highlighting the need for prospective outcome-focused studies to define the role for MRgRT within multimodality treatment pathways. Full article

Background/Objectives: MR-guided radiation therapy (MRgRT) has rapidly evolved into an important treatment modality, with the Elekta Unity and ViewRay MRIdian systems being two major MR-linac platforms. Despite the shared concept of MRgRT, the two platforms elected different system designs that could potentially impact the dosimetric characteristics and quality of a treatment. In this study, we aim to perform a comparative dosimetric investigation between these two MR-linac systems in prostate and pancreas cancers. Methods: Dosimetric characteristics were evaluated by retrospectively re-creating 20 clinical prostate and pancreas cases originally treated on MRIdian using the Unity system, adhering to MIRAGE and SMART clinical trial constraints. Treatment plans were re-created with matching planning images, structures, beam geometry, and dose parameters. To ensure comparison consistency, all Unity treatment plans were normalized to match the target coverage of the MRIdian counterparts, and the organ-at-risk (OAR) dose was investigated. Results: Most OARs’ dose-volume metrics showed no statistically significant differences. For prostate patients, Unity demonstrated lower rectum V36Gy (p = 0.0095), V38Gy (p = 0.0043), V40Gy (p = 0.0469), and lower left (p = 0.0137) and right femur V20Gy (p = 0.0020). For pancreas patients, Unity plans had a lower mean liver dose (p = 0.0371). All Unity plans had a Gamma passing rate > 90%, confirming the clinical deliverability. Mean delivery times were 12.78 ± 1.68 and 13.53 ± 1.88 min for MRIdian and Unity prostate plans, respectively, and 14.58 ± 2.78 and 17.40 ± 3.77 min for MRIdian and Unity pancreas plans, respectively. Conclusions: Overall, comparable treatment quality and delivery times were observed between the two platforms. Full article

Advances in breast cancer treatment have shifted the focus from maximizing local control to balancing oncologic efficacy with treatment de-escalation and toxicity reduction. Whole-breast irradiation (WBI) following breast-conserving surgery remains the standard of care, but with up to 90% of recurrences occurring near the tumor bed, partial breast irradiation (PBI) has emerged as a viable alternative. Large randomized controlled trials (such as IMPORT LOW, Florence, and GEC-ESTRO) have demonstrated comparable ipsilateral breast tumor recurrence (IBTR) rates between PBI and WBI, reinforcing its oncologic safety in well-selected patients. However, challenges remain in optimizing fractionation schedules, refining patient selection, and minimizing late toxicity. Recent innovations, including MRI-guided radiotherapy (MRgRT) and neoadjuvant PBI, offer improved tumor targeting, real-time plan adaptation, and enhanced normal tissue sparing. These advancements hold promise for further reducing radiation-related morbidity and improving cosmetic outcomes. As PBI progresses, integrating novel imaging modalities and hypofractionated regimens will be crucial to refining protocols. This review synthesizes the latest evidence on PBI techniques, clinical outcomes, and emerging technologies to guide future research and clinical decision-making in precision breast radiotherapy. Full article

Background/Objectives: Stereotactic body radiotherapy is frequently used in patients with adrenal metastases. Motion of adherent radiosensitive organs at risk (OARs) and tumors influence OAR toxicity and tumor control. Online-adaptive Magnetic Resonance-guided radiotherapy (MRgRT) can address and mitigate interfractional changes. However, the impact of intrafractional variations in adrenal MRgRT is unknown. Methods: A total of 23 patients with 24 adrenal metastases were treated with MRgRT. After daily plan adaptation and before beam application, an additional (preRT) 3d MRI was acquired. PreRT target volumes and OARs were retrospectively recontoured in 200 fractions. The delivered, online-adapted treatment plans, as well as non-adapted baseline plans, were calculated on these re-contoured structures to quantify the dosimetric impact of intrafractional variations on target volume coverage and OAR doses with and without online adaptation. Normal tissue complication probabilities (NTCPs) were calculated. Results: The median time between the two MRIs was 56.4 min. GTV and PTV coverage (dose to 95% of the PTV, D95%, and volume covered by 100% of the prescription dose, V100%) were significantly inferior in the preRT plans. GTV D_mean was significantly impaired in left-sided metastases, but not in right-sided metastases. Compared to non-adapted preRT plans, adapted preRT plans were still significantly superior for all GTV and PTV metrics. Intrafractional violations of OAR constraints were frequent. D0.5cc and the volume exposed to the near-maximum dose constraint were significantly higher in the preRT plans. The volume exposed to the D0.5cc constraints in single fractions escalated up to 1.5 cc for the esophagus, 3.2 cc for the stomach, 5.3 cc for the duodenum and 7.3 cc for the bowel. This led to significantly elevated NTCPs for the stomach, bowel and duodenum. Neither PTV D95%, nor gastrointestinal OAR maximum doses were significantly impaired by longer fraction duration. Conclusions: Intrafractional motion in adrenal MRgRT caused significant impairment of target volume coverage (D95% and V100%), potentially undermining local control. Frequent violation of gastrointestinal OAR constraints led to elevated NTCP. Compared to non-adaptive treatment, online adaptation still highly improved GTV and PTV coverage. Full article

Background/Objectives: Over the past decade, significant advances have been made in image-guided radiotherapy (RT) particularly with the introduction of magnetic resonance (MR)-guided radiotherapy (MRgRT). However, the optimal clinical applications of MRgRT are still evolving. The intent of this analysis was to describe our institutional MRgRT utilization patterns and evolution therein, specifically as an early adopter within a center endowed with multiple other technology platforms. Materials/Methods: We retrospectively evaluated patterns of MRgRT utilization for patients treated with a 0.35-Tesla MR-Linac at our institution from April 2018 to April 2024. We analyzed changes in utilization across six annualized periods: Period 1 (April 2018–April 2019) through Period 6 (April 2023–April 2024). We defined ultra-hypofractionation (UHfx) as 5 or fewer fractions with a minimum fractional dose of 5 Gy. Electronic health records were reviewed, and data were extracted related to patient, tumor, and treatment characteristics. Results: A total of 823 treatment courses were delivered to 712 patients treated for 854 lesions. The most commonly treated sites were the pancreas (242 [29.4%]), thorax (172; 20.9%), abdominopelvic lymph nodes (107; 13.0%), liver (72; 8.7%), and adrenal glands (68; 8.3%). The median total prescribed dose of 50 Gy in five fractions (fxs) was typically delivered in consecutive days with automatic beam gating in inspiration breath hold. The median biologically effective dose (α/β = 10, BED10) was 94.4 Gy with nearly half (404, 49.1%) of all courses at a prescribed BED10 ≥ 100 Gy, which is widely regarded as a highly effective ablative dose. Courses in Period 6 vs. Period 1 more often had a prescribed BED10 ≥ 100 Gy (60.2% vs. 41.6%; p = 0.004). Of the 6036 total delivered fxs, nearly half (2643, 43.8%) required at least one fx of on-table adaptive radiotherapy (oART), most commonly for pancreatic tumors (1081, 17.9%). UHfx was used in over three quarters of all courses (630, 76.5%) with 472 (57.4%) of these requiring oART for at least one fraction. The relative utilization of oART increased significantly from Period 1 to Period 6 (37.6% to 85.0%; p < 0.001); a similar increase in the use of UHfx (66.3% to 89.5%; p < 0.001) was also observed. The median total in-room time for oART decreased from 81 min in Period 1 to 45 min in Period 6, while for non-oART, it remained stable around 40 min across all periods. Conclusions: Our institution implemented MRgRT with a priority for targeting mobile extracranial tumors in challenging anatomic locations that are frequently treated with dose escalation, require enhanced soft-tissue visualization, and could benefit from an ablative radiotherapy approach. Over the period under evaluation, the use of high-dose ablative doses (BED10 ≥ 100 Gy), oART and UHfx (including single-fraction ablation) increased significantly, underscoring both a swift learning curve and ability to optimize processes to maximize throughput and efficiency. Full article

Approximately 36% of patients with cervical cancer present with regional nodal metastasis at diagnosis, which is associated with adverse survival outcomes after definitive treatment. In the modern era of chemoradiotherapy (CRT) and image-guided adaptive brachytherapy (IGABT), where excellent local control is achieved for patients with locally advanced cervical cancer (LACC), nodal failure remains a major challenge to cure. To optimize treatment outcomes for node-positive LACC and reduce the incidence of nodal failure, various treatment approaches have been explored, including methods of surgical nodal staging or dissection, RT dose escalation strategies, such as intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to involved nodes, and elective treatment of subclinical para-aortic (PAO) disease. Additionally, there is growing interest in emerging precision RT techniques, such as magnetic resonance-guided radiotherapy (MRgRT) and proton therapy, which may allow for further improvement in the therapeutic ratio. This review outlines the various methods of detection of nodal metastasis, treatment options for node-positive LACC, techniques of nodal radiotherapy and their clinical evidence in efficacy and toxicity profiles. Furthermore, recent advances in systemic therapy and promising novel therapeutic directions that may shape the management of node-positive LACC are discussed. Full article

Background/Objectives: Advancements in radiotherapy technology now enable the delivery of ablative doses to targets in the upper urinary tract, including primary renal cell carcinoma (RCC) or upper tract urothelial carcinomas (UTUC), and secondary involvement by other histologies. Magnetic resonance imaging-guided linear accelerators (MR-Linacs) have shown promise to further improve the precision and adaptability of stereotactic body radiotherapy (SBRT). Methods: This single-institution retrospective study analyzed 34 patients (31 with upper urinary tract non-metastatic primaries [RCC or UTUC] and 3 with metastases of non-genitourinary histology) who received SBRT from August 2020 through September 2024 using a 1.5 Tesla MR-Linac system. Treatment plans were adjusted by using [online settings] for “adapt-to-position” (ATP) and “adapt-to-shape” (ATS) strategies for anatomic changes that developed during treatment; compression belts were used for motion management. Results: The median duration of treatment was 56 min overall and was significantly shorter using the adapt-to-position (ATP) (median 54 min, range 38–97 min) in comparison with adapt-to-shape (ATS) option (median 80, range 53–235 min). Most patients (77%) experienced self-resolving grade 1–2 acute radiation-induced toxicity; none had grade ≥ 3. Three participants (9%) experienced late grade 1–2 toxicity, potentially attributable to SBRT, with one (3%) experiencing grade 3. Conclusions: We conclude that MR-Linac-based SBRT, supported by online plan adaptation, is a feasible, safe, and highly precise treatment modality for the definitive management of select upper urinary tract lesions. Full article

Radiotherapy, a crucial technique in cancer therapy, has traditionally relied on the premise of largely unchanging patient anatomy during the treatment course and encompassing uncertainties by target margins. This review introduces adaptive radiotherapy (ART), a notable innovation that addresses anatomy changes and optimizes the therapeutic ratio. ART utilizes advanced imaging techniques such as CT, MRI, and PET to modify the treatment plan based on observed anatomical changes and even biological changes during the course of treatment. The narrative review provides a comprehensive guide on ART for healthcare professionals and trainees in radiation oncology and anyone else interested in the topic. The incorporation of artificial intelligence in ART has played a crucial role in improving effectiveness, particularly in contour segmentation, treatment planning, and quality assurance. This has expedited the process to render online ART feasible, lowered the burden for radiation oncology practitioners, and enhanced the precision of dynamically personalized treatment. Current technical and clinical progress on ART is discussed in this review, highlighting the ongoing development of imaging technologies and AI and emphasizing their contribution to enhancing the applicability and effectiveness of ART. Full article

Technological advances in radiation oncology are oriented towards improving treatment precision and tumor control. Among these advances, magnetic-resonance-image-guided radiation therapy (MRgRT) stands out, with technological advances to deliver targeted treatments adapted to a tumor’s anatomy on the day while minimizing incidental exposure to organs at risk, offering an unprecedented therapeutic advantage compared to X-ray-based IGRT delivery systems. This new technology changes the traditional workflow in radiation oncology and requires an evolution in team coordination to administer more precise treatments. Once implemented, it paves the way for newer indication for radiation therapy to safely deliver higher doses than ever before, with better preservation of healthy tissues to optimize patient outcomes. In this narrative review, we assess the technical aspects of the novel linear accelerators that can deliver MRgRT and summarize the available published experience to date, focusing on oncological results and future challenges. Full article

Magnetic resonance imaging (MRI) provides excellent visualization of central nervous system (CNS) tumors due to its superior soft tissue contrast. Magnetic resonance-guided radiotherapy (MRgRT) has historically been limited to use in the initial treatment planning stage due to cost and feasibility. MRI-guided linear accelerators (MRLs) allow clinicians to visualize tumors and organs at risk (OARs) directly before and during treatment, a process known as online MRgRT. This novel system permits adaptive treatment planning based on anatomical changes to ensure accurate dose delivery to the tumor while minimizing unnecessary toxicity to healthy tissue. These advancements are critical to treatment adaptation in the brain and spinal cord, where both preliminary MRI and daily CT guidance have typically had limited benefit. In this narrative review, we investigate the application of online MRgRT in the treatment of various CNS malignancies and any relevant ongoing clinical trials. Imaging of glioblastoma patients has shown significant changes in the gross tumor volume over a standard course of chemoradiotherapy. The use of adaptive online MRgRT in these patients demonstrated reduced target volumes with cavity shrinkage and a resulting reduction in radiation dose to uninvolved tissue. Dosimetric feasibility studies have shown MRL-guided stereotactic radiotherapy (SRT) for intracranial and spine tumors to have potential dosimetric advantages and reduced morbidity compared with conventional linear accelerators. Similarly, dosimetric feasibility studies have shown promise in hippocampal avoidance whole brain radiotherapy (HA-WBRT). Next, we explore the potential of MRL-based multiparametric MRI (mpMRI) and genomically informed radiotherapy to treat CNS disease with cutting-edge precision. Lastly, we explore the challenges of treating CNS malignancies and special limitations MRL systems face. Full article

Magnetic resonance-guided radiotherapy (MRgRT) represents a promising new image guidance technology for radiation treatment delivery combining an onboard MRI scanner with radiation delivery technology. By enabling real-time low-field or high-field MRI acquisition, it facilitates improved soft tissue delineation, adaptive treatment, and motion management. Now that MRgRT has been available for nearly a decade, research has shown the technology can be used to effectively shrink treatment margins to either decrease toxicity (in breast, prostate cancer, and pancreatic cancer) or facilitate dose-escalation and improved oncologic outcomes (in pancreatic and liver cancer), as well as enabling indications that require clear soft tissue delineation and gating (lung and cardiac ablation). In doing so, the use of MRgRT has the potential to significantly improve the outcomes and quality of life of the patients it treats. The present narrative review aims to describe the rationale for MRgRT, the current and forthcoming state of technology, existing studies, and future directions for the advancement of MRgRT, including associated challenges. Full article

Stereotactic body radiotherapy (SBRT) is an effective radiation therapy technique that has allowed for shorter treatment courses, as compared to conventionally dosed radiation therapy. As its name implies, SBRT relies on daily image guidance to ensure that each fraction targets a tumor, instead of healthy tissue. Magnetic resonance imaging (MRI) offers improved soft-tissue visualization, allowing for better tumor and normal tissue delineation. MR-guided RT (MRgRT) has traditionally been defined by the use of offline MRI to aid in defining the RT volumes during the initial planning stages in order to ensure accurate tumor targeting while sparing critical normal tissues. However, the ViewRay MRIdian and Elekta Unity have improved upon and revolutionized the MRgRT by creating a combined MRI and linear accelerator (MRL), allowing MRgRT to incorporate online MRI in RT. MRL-based MR-guided SBRT (MRgSBRT) represents a novel solution to deliver higher doses to larger volumes of gross disease, regardless of the proximity of at-risk organs due to the (1) superior soft-tissue visualization for patient positioning, (2) real-time continuous intrafraction assessment of internal structures, and (3) daily online adaptive replanning. Stereotactic MR-guided adaptive radiation therapy (SMART) has enabled the safe delivery of ablative doses to tumors adjacent to radiosensitive tissues throughout the body. Although it is still a relatively new RT technique, SMART has demonstrated significant opportunities to improve disease control and reduce toxicity. In this review, we included the current clinical applications and the active prospective trials related to SMART. We highlighted the most impactful clinical studies at various tumor sites. In addition, we explored how MRL-based multiparametric MRI could potentially synergize with SMART to significantly change the current treatment paradigm and to improve personalized cancer care. Full article

Liver stereotactic body radiotherapy (SBRT) is a local treatment that provides good local control and low toxicity. We present the first clinical results from our prospective registry of stereotactic MR-guided radiotherapy (MRgRT) for liver metastases. All patients treated for liver metastases were included in this prospective registry study. Stereotactic MRgRT indication was confirmed by multidisciplinary specialized tumor boards. The primary endpoints were acute and late toxicities. The secondary endpoints were survival outcomes (local control, overall survival (OS), disease-free survival, intrahepatic relapse-free survival). Twenty-six consecutive patients were treated for thirty-one liver metastases between October 2019 and April 2022. The median prescribed dose was 50 Gy (40–60) in 5 fractions. No severe acute MRgRT-related toxicity was noted. Acute and late gastrointestinal and liver toxicities were low and mostly unrelated to MRgRT. Only 5 lesions (16.1%) required daily adaptation because of the proximity of organs at risk (OAR). With a median follow-up time of 17.3 months since MRgRT completion, the median OS, 1-year OS and 2-year OS rates were 21.7 months, 83.1% (95% CI: 55.3–94.4%) and 41.6% (95% CI: 13.5–68.1%), respectively, from MRgRT completion. The local control at 6 months, 1 year and 2 years was 90.9% (95% CI: 68.3–97.7%). To our knowledge, we report the largest series of stereotactic MRgRT for liver metastases. The treatment was well-tolerated and achieved a high LC rate. Distant relapse remains a challenge in this population. Full article